Caging of pharmacologically active compounds is an interesting approach in biological chemistry and such photoactivatable compounds are also being developed towards novel therapeutic prodrug concepts. In this study we investigated the photolysis of the commonly used 4,5‐dimethoxy‐2‐nitrobenzyl (DMNB) caging moiety attached to the NH‐nitrogen of the pharmacologically relevant N‐phenylpyrimidine‐2‐amine scaffold. Based on this concept, a small set of para‐phenyl substituted derivatives with varying I/M effects (inductive/mesomeric electron‐donating/withdrawing effects) was designed, synthesized and parameters of the photolysis were determined. Hammett constants were related to photokinetic measurements, revealing electron donating effects to be unfavorable for the photolysis reaction. Our findings suggest electronic features of the entire molecule should be taken into account when considering its suitability for the caging concept. The results may also serve as a guideline to make relevant choices for DMNB applications in classical protecting group chemistry.

中文翻译：

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电子效应对光解的影响：4,5-二甲氧基-2-硝基苄基笼中的N-苯基嘧啶-2-胺支架的模型研究

笼罩药理活性化合物是生物化学中一种有趣的方法，并且这种可光活化化合物也正朝着新的治疗前药概念发展。在这项研究中，我们研究了常用的4,5-二甲氧基-2-硝基苄基（DMNB）笼罩部分的光解作用，该笼罩部分与药理相关的N-苯基嘧啶-2-胺骨架的NH-氮相连。基于此概念，设计，合成了一小组具有不同I / M效应（感应/介电子给电子/吸电子效应）的对苯基取代衍生物，并确定了光解参数。哈米特该常数与光动力学测量有关，表明给电子作用对光解反应不利。我们的发现表明，在考虑其适合笼养概念时应考虑整个分子的电子特征。该结果还可作为指导，为DMNB在经典保护基化学中的应用做出相关选择。